THE  PREPARATION  OF  GLYCOLS 


BY 


ALBERT  LEWIS  TANENBAUM 


THESIS 


FOR  THE 


DEGREE  OF  BACHELOR  OF  SCIENCE 


IN 

CHEMICAL  ENGINEERING 


COLLEGE  OF  LIBERAL  ARTS  AND  SCIENCES 


UNIVERSITY  OF  ILLINOIS 


1922 


\"J  (AsU* 


UNIVERSITY  OF  ILLINOIS 


t r , Tt  04  If'';'' 

192 


THIS  IS  TO  CERTIFY  THAT  THE  THESIS  PREPARED  UNDER  MY  SUPERVISION  BY 

Albert  Lewis  T an e nbaurr. 


ENTITLED T 


ratie*'*  0 t nivoc^  s 


IS  APPROVED  BY  ME  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR  THE 
degree  of ? chjslor of_ _ B_cience _ _i n Ch_e rn i 2 I 


(2-CaaJL.  _ : 

Instructor  in  Charge 


Approved  : 


HEAD  OF  DEPARTMENT  OF 


500260 


Digitized  by  the  Internet  Archive 
in  2015 


https://archive.org/details/preparationofglyOOtane 


THE  PKBPaHAI1  I OB  GY  GLYCOLS 


I wish  to  extend  mp-  sincere  thanks  and 
appreciation  to  Dr.  C*  o*  Llarvel,  under 
whose  supervision  this  work  was  done, 
for  helpful  suggestions  and  interest 
shown  during  the  experimental  work* 


Pable  of  Contents 


Page 

Introduction  1 

theoretical  £ 

Experimental 

Phenoxy  propyl  magnesium  bromide  5 

^‘-ch.lorpropionic  acid  6 

phenoxy  propyl  cyanide  6 

Ethyl  t«*phenoxy  butyrate  7 

Phenoxy  butyl  alcohol  9 

% -Phenoxy  butyl  b-nitrobenzoate  11 

Phenoxy  butyl  bromide  12 

fetrame thylene  bromide  12 

Summary  14 

Bibliography  15 


Introduction 


This  work  was  undertaken  with,  the  purpose  of  synthesizing 
phenoxy  butyl  bromide  and  tetramethylene  bromide  by  a method 
that  would  make  use  of  comparatively  cheap  and  readily  access- 
ible materials* 

Ethylene  bromide,  trimethylene  bromide,  and  pentamethylene 
bromide  can  be  obtained  at  a reasonable  cost.  The  preparation 
of  tetramethylene  bromide  would  fill  the  gap  in  this  series  of 
valuable  reagents,  ^leo,  it  was  wanted  in  this  laboratory  as 
an  intermediate  in  the  preparation  of  anaesthetics. 

Phenoxy  ethyl  and  phenoxy  propyl  bromides  can  be  prepared 
in  good  yields  from  sodium  phenolate  and  ethylene  and  trimethyl- 
ene bromides,  respectively.  Phenoxy  butyl  bromide  held  a 
special  interest,  at  this  time,  since  it  was  to  be  used  in  the 
preparation  of  derivatives  of  lysine. 


2 


Theoretical  and  historical 


Tetramethylene  "bromide  was  first  prepared  "by  Guetavson  and 
Dem^anoff • by  recluotic  " ethylene  cyanide  to  tetr amethylene 
diamine,  and  subsequent  treatment  with  silver  nitrite  to  form 
tetramethylene  glycol,  which  was  split  with  hydro  bromic  acid* 

The  yield  was  exceptionally  low* 

Hammonet^  prepared  it  by  electrolyzing  the  potassium  salt 
of  ^-amyloxypropionic  acid#  The  1,4  diamyloxybutane  formed  was 
split  by  means  of  hydrobromic  acid. 

J.  V.  Braun  and  BeschheS  synthesized  tetramethylene  bromide 
by  means  of  the  following  series  of  reactions: 


These  methods  of  preparation,  may  be  used  when  only  small 
-.mounts  of  the  product  are  desired,  but  a cheaper  method  would 
allow  the  use  of  it  in  larger  amounts. 

Since  phenoxy  propyl  bromide  is  a comparatively  cheap  re- 
agent now,  it  was  decided  to  prepare  the  Grignard  reagent  of 
this  compound  and  treat  it  with  formaldehyde,  which  should  form 
phenoxy  butyl  alcohol.  This  could  be  converted  into  the  mono  and 


< 


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dibromo  compounds.  -a  mixture  of  products  wes  formed,  from  which 
phenoxy  "butyl  alcohol  could  not  be  isolated* 

attempt  was  then  made  to  prepare  the  product  desired  by 
treating  the  Grignard  reagent  with  mono -chi or-methyl  ether,  a 
modification  of  a method  used  by  hammonet,  but  it  was  found  thft 
in  this  case  also,  the  product  obtained  was  a mixture  of  many 
compounds. 

Both  the  results  obtained,  and  the  fact  that  an  equivalent 
amount  of  magnesium  vxmld  not  react  with  the  halide,  suggested 
the  i ossibility  that  the  Grignard  reagent  was  only  forming  to  a 
limited  extent,  To  prove  this  contention,  the  Grignard  reagent 
v/as  treated  with  water.  The  amount  of  phenyl  propyl  ether  formed 
would  be  an  indication  of  the  amount  of  Grignard  reagent  formed. 
a compound,  boiling  at  185-186°,  was  isolated  from  the  reaction 
mixture.  The  yield  was  about  20^  theory.  Since  the  phenoxy 
propyl  magnesium  bromide  formed  only  to  such  a slight  extent,  it 
was  decided  to  drop  this  method  for  the  preparation  of  the 
desired  products. 

It  was  decided  to  prepare  phenoxy  propionic  acid,  which 
should  form,  by  the  electrolysis  of  its  potassium  salt,  1,4  &i- 
phenoxy  butane.  This  acid  could  be  prepared  much  more  cheaply 
than  the  one  used  by  hammonet  and  might  give  better  yields. 

Trimethylene  chlorhydrin  has  recently  become  available  for 
use,  through  its  preparation  from  trimethylene  glycol.  The 
oxidation  product  of  tmis  compound,  fc-chlor  propionic  acid, 


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-4- 


oould  be  treated  with.  30dium  phenolate  to  give  the  phenoxy 
propionic  acid.  ^lso,  since  B-ohlorpropionio  acid  is 
valuable  reagent,  the  department  was  interested  in  developing 
the  proceedure  for  this  preparation*  iiuns  were  made  under 
various  conditions,  but  the  best  procedure  was  not  determined, 
since  this  method  of  preparing  tetramethylene  bromide  and  phenoxy 
butyl  bromide  was  dropped  in  favor  of  the  method,  described  be- 
low, which  seemed  to  have  greater  possibilities® 

The  starting  point  for  this  method  was  phenoxy  propyl 
bromide.  It  had  been  converted,  in  our  laboratory,  into  phenoxy 
propyl  cyanide  in  72$  yields.  Phis  yield  was  increased  to  95- 
95$.  The  cyanide  was  than  converted  into  e thy 1-S -phenoxy 
butyrate,  in  80$  yields,  which  was  reduced  to  the  corresponding 
alcohol  by  a modification  of  the  method  of  levene  and  Allens 
The  time  of  reduction  was  reduced  to  fifteen  minutes,  the  total 
time  needed  for  the  reduction  of  100  g*  of  the  ester  being  about 
five  hours.  Of  this,  three  hours  was  t alien  up  in  allowing  the  &1« 
cohol  and  toluene  to  distill  from  the  reaction  mixture,  file 
yield  was  62-*68$  theory*  The  phenoxy  butyl  alcohol  was  then 
treated  with  phosphorous  tribromide  in  order  to  prepare  phenoxy 
butyl  bromide.  Treatment  of  the  alcohol  with  48$  hydro bromic 
acid  gave  a mixture  of  tetramethylene  bromide  and  phenoxy  butyl 
bromide.  The  desired  products  can  be  prepared  by  this  method  in 
fc.ir  yields  and  at  a reasonable  cost® 


PliEUGXY  PflOPYL  llaGuBSIUk  BBOLilDE 

In  a 1 1. round-tot tom  flask,  fitted  with  an  upright  con- 
denser 300  c.c.  of  dry  ether,  11.5  g.  of  magnesium  and  a crystal 
of  iodine  were  placed*  100  g.  of  phenoxy  propyl  bromide  were 
tnen  added  over  a period  of  one  hour.  The  reaction  seemed  to 
run  smoothly  except  that  only  about  one  half  of  the  magnesium 
reacted,  and  some  magnesium  bromide  separated  out. 

an  equivalent  amount  of  trioxymethylene  was  added  to  the 
drignard  reagent,  and  the  mixture  heated  on  the  steam  bath  for 
three  hours.  Water  and  enough  hydrochloric  acid  to  dissolve  the 
precipitated  solids  were  added  and  the  ether  l^yer  separated, 
^fter  distilling  the  ether  the  residue  was  distilled  under  di- 
minished pressure.  It  boiled  from  95°  to  170°  under  twenty 
vnm.  pressure,  no  clear  cut  fractions  being  obtained* 

To  another  run  of  the  Grignard  reagent  an  equivalent  amount 
of  monochlor  methyl  ether  7/as  added,  The  reaction  mixture  was 
treated  in  the  same  manner  as  described  above,  but  the  product 
could  not  be  separated  into  definite  fractions. 

To  still  another  run  of  the  Grignard  reagent  water  was 
added,  and  the  product  obtained  distilled  very  carefully.  Small 
fractions  of  unsaturated  compounds  and  a phenol  were  obtained. 
The  highest  boiling  fraction  turned  solid  on  cooling.  It  was 
assumed  to  be  diphenoxy  hexane.  The  largest  fraction  boiled  at 


185-185°  at  atmospheric  pressure.  Its  specific  gravity  was 


* 


4 


-6- 


.941$£°  and  index  of  refraction  1*5012  at  25°.  It  was  assumed 
4U 

to  be  phenyl  propyl  ether,  which  toils  at  183*9°  and  has  a 
specific  gravity  of  .9459^^*  f he  yield  was  12  g*  (20^j)  theory* 


IhLUR  PhOPIOxv'IG  aGXD 

In  a 31.  round -hot tom  flask  fitted  with  a mechanical 
stirrer,  upright  condenser  and  dropping  funnel  were  placed  350 
g.  of  fuming  nitric  acid.  120  g.  of  trimat hylene  chlorhydrin 
were  added  slowly  through  the  dropping  funnel ( about  two  hours). 
When  the  temperature  of  the  reaction  mixture  rose  to  about  35° 
(in  ten-.  en  minutes* ),  An  ice  bath( about  5-10°)  was  placed 
around  the  flask*  After  the  addition  of  the  chlorhydrin,  the 
reaction  mixture  was  stirred  for  three  hours.  It  was  then 
allowed  to  stand  at  room  temperature  overnight.  Water (300  c.c.) 
was  added  to  the  mixture  and  the  &.chlorpropionic  acid  extracted 
with  ether,  The  acid  was  distilled  under  diminished  pressure. 

76  grams(55fj)  of  the  acid  were  obtained.  P.P.  106-107  at  eeven- 
mm.  ; 112-114  at  twenty~tw(  *nw.  ; 115-116  at  twenty- 
sJb  The  acid  solidified  on  cooling (h. I.  41°). 

The  reaction  will  not  take  place  in  a freezing  mixture® 
at  room  temperature  the  reaction  is  so  vigorous  that  the 
contents  of  the  flask  are  lost  through,  the  condenser  tube. 

PiiMOXY  PhGPYL  C Yah  IDE5 
C » 0 » ( GE  , ) (B  ■+..  CH  1 ^ \ ) w*  + 


-7- 


In  a 5 1*  round-tot tom  flask  fitted  witli  a reflux  condenser, 
1000  g.  of  phenoxy  propyl  bromide,  325  g*  of  sodium  cyanide,  325 
g#  of  water,  and  500  g.  of  ethyl  alcohol(  95fj)  were  placed.  Che 
flask  was  heated  on  a steam  bath  for  from  fifteen  to  twenty  hours. 
Che  heat  was  so  regulated  that  the  reaction  mixture  refluxed 
rather  rapidly.  Che  flask  v/as  then  cooled  and  about  800  cc.  of 
ether  added.  Che  ether  layer,  containing  the  small  amount  of 
unchanged  phenoxy  propyl  bromide  and  the  cyanide,  was  decanted. 

Che  water  layer  was  then  extracted  with  about  100  c.c.  of  ether, 
which  was  added  to  the  first  ether  portion.  Che  ether  was  dis- 
tilled on  a steam  bath{  to  a volume  of  about  800-900  c.c.)  and 
the  residue  decanted  from  the  small  amount  of  inorganic  salt 
that  separated  out.  Che  residue  v/as  distilled  under  diminished 
pressure.  ^ small  amount  of  the  bromide  passed  over  at  about 
148°  at  23  mm. (159°  at  34  ram*).  Che  water-white  phenoxy  propyl 
cyanide  then  distilled  over.  (B*P.  162-166  at  £2  mm.;  172-175  at  3f 
mm.)  695-711  g.  of  phenoxy  propyl  cyanide  were  obtained( 93-95'^ 
t he  ory ) • 


It  is  not  advisable  to  reflux  for  a shorter  tine  if  maximum 
yield  is  desired. 

JCCAa  h'uCYxu.Ch 


EOgH-.G* ( CHg)  3U+2C  - + SC  *2H  C — ^CgH^QfOH  )3C00CgH5 


(ITH  ) 30 
4 2 4 


\ l 


In  a 5-1  round-bottom  flask,  fitted  with  en  efficient 
reflux  condenser , were  placed  625  g.  of  95^  alcohol,  509  c.e* 
of  cone*  sulfuric  acid(  ap*  gr . 1.84)and  S00  g«  phenoxy 
cyanide.  She  mixture  was  then  heated  and  kept  refluxing  for 
seven  hours*  The  flask  was  then  cooled,  which  caused,  the 
ammonium  sulfate  to  separate  out  and  the  ester  to  come  to  the 
top.  The  liquid  contents  were  poured  into  a separatory  funnel 
and  the  water  layer  drawn  off  into  the  flask  containing  the 
ammonium  sulfate.  The  ester  layer  was  washed  with  a dilute 
sodium  carbonate  solution  to  remove  small  amounts  of  phenoxy 
butyric  acid  that  might  have  been  present.  Enough  water  was 
added  to  dissolve  the  ammonium  sulfate,  and  this  was  extracted 
with  ether,  which  was  washed  with  a dilute  sodium  carbonate 
solution  said  then  added  to  the  ester.  The  ester  was  distilled 
under  diminished  pressure.  Yield  510-516  g.( 79-80^  theory). 

B.  P.  160-168°  at  25  mm.,  168-174°  at  27  mm.,  178-184°  at  40  mm. 
Index  of  refraction  1.498  at  27°. 

Analysis;  wt,  of  sample  .4410  grams 

Obtained  861*6  c.c.  of  GG&  at  52.0°  an<*  Va].:  an. 

Q.  pound  68.95  Calc*  69.19 

jx  white  curdy  solid  sometimes  separated  out  during  the 
distillation,  but  this  had  no  effect  upon  the  yield  or  purity 
of  the  product.  It  seems  as  if  more  of  this  solid  would  separ- 
ate out  if  the  reaction  mixture  was  thrown  into  water  and  ex- 


tracted with  ether* 


-9 


I"  l -rt i * S /CY  EUlfiTZi  xijjOuxiOX 

Xc,xxc  • w • ( GHp ) rrOOOOpxxir__iX± — ■ — y O5K5  • 0 • ( Xxxc> ) ^CxIgOh. 
D J fv  u C 1 _ H — Un 


2he  apparatus  consisted  of 
a 5-1.  round-bottom  flask  fitted 
with  a rubber  stopper,  holding  a 
mechanical  stirrer,  3/4  inch 
tube,  and  separatory  funnel,  fhe 
tube  was  bent  just  outside  of  the 
stopper  at  an  angle  correspond- 
ing to  that  at  which  the  con- 
denser was  to  be  set (about  45°). 

I he  tube  was  connected  to  a sin 
foot  condenser ( by  means  of  a rubber  connection) having  a con- 
denser tube  5/4  inch  in  diameter,  phis  proved  oo  j3  a T^ry 
efficient  arrangement  as  the  liquid  -lowed  back  on  one  side 
of  the  tube  while  the  vapors  flowed  up  the  other  side. 

110  grams  of  sodium  and  200  c.c.  of  dry  toluene  were 
"olaced  in  the  flask  and  heateci  in  an  oil  batu  un>jil  tne  oOdium 
was  melted.  Jhe  stirrer  was  then  rotated  vigorously  and  as 
soon  as  the  sodium  was  in  a finely  divided  state,  the  oil 
bath  was  removed.  <Yhile  the  flask  was  cooling,  the  stirrer 
was  run  continuously.  2he  sodium  solidified  into  small  solid 
particles  which  were  kept  mijwed  with  the  toluene  by  means  of 


-10- 


tlie  stirrer.  An  ice  bath  was  then  placed  around  the  flask*  a 
uinf'.ro  of  100  g.  of  ethyl  S-phenoxy  butyrate  and  100  c.c.  of 
absolute  alcohol  were  added.  This  might  have  been  added  as 
rapidly  as  the  condenser  was  capable  of  condensing  the  alcohol 
vapor(from  2 to  2 1/2  min.),  fhe  ice  bath  was  txen  removed, 
otherwise  the  sodium  ethylate  would  form  solid  cakes*  500  c.c. 
of  absolute  alcohol  wsre  then  run  in  at  such  a rate  that  the 
contents  of  the  flask  remained  mushy,  fhe  total  time  consumed 
up  to  this  point  was  about  15-20  min.  3y  this  time  most  of 
the  sodium  would  have  been  consumed,  but  the  reaction  was 
allowed  to  proceed  for  15  minutes  longer# 

I 

About  300  c.c.  of  water  were  then  added(in  about  5 min.) 
until  everything  was  in  solution,  fhe  oil  bath  was  replaced 
and  the  mixture  refluxed  for  30  minutes  in  order  to  saponify 
any  small  amount  of  unconverted  ester  that  might  have  remained. 

^fter  refluxing,  the  flask  v7as  connected  by  a fraction- 
ating tube  to  a condenser  set  for  downward  distillation,  and 
the  alcohol  and  toluene  distilled  completely  from  a steam  bath. 
Enough  water  was  added  to  dissolve  the  solid  that  separated 
out,  and  the  solution  was  extracted  twice  with  ether,  fhe 
ether  layers  ?/ere  washed  with  water,  combined,  and  the  ether 
distilled,  fhe  residue  was  distilled  under  diminished  pressure, 
fne  forerun,  con  Lng  of  a little  e . , water,  and  toluene, 
was  discarded.  Yield  of  phenoxy  butyl  alcohol,  50-54  grams 
( 62-68/  theory).  B.p*  162-154°  at  19  mm.,  166-1680  at  24  m. 


-11- 


Index  of  refraction  1*520  at  27°. 

Analysis:  Wt.  of  sample  .4470  grams 

Obtained  751*0  of  GO  at  32.5°  and  738*5  ram* 

G.  ffound  72.22  Calc.  72.24 

Ale  ohol(  which  had  been  distilled  over  lime) was  distilled 
over  enough,  sodium  to  take  up  the  remaining  water* 
loluene  was  dried  over  sodium. 

fhe  ester  was  kept  over  anhydrous  sodium  sulfate, 
fhe  closer  the  stirrer  to  the  bottom  of  the  flask,  the 
greater  the  subdivision  of  the  sodium* 

ah  ice  bath  should  at  all  times  be  handy  during  the  re- 
duction. If  the  reaction  becomes  too  vigorous  and  the  alcohol 
shoots  up  into  the  condenser,  stopping  the  stirrer  and  placing 
an  ice  bath  around  the  flask  will  usually  stop  this  action. 

Good  yields  can  be  obtained  only  when  the  apparatus  and 
materials  are  absolutely  dry. 

Occasionally  yields  as  high  as  75;]  have  been  obtained. 
Other  methods  cf  extraction  have  been  tried  but  the 
method  described  is  easiest  of  operation  and  gives  the  best 
yields. 

S-MMOXY  [ ^UIESOBE^S  0 A 

10  gi  of  k-nitro  benzo2rl  chloride  and  phenoxy  butyl 
alcohol  in  slight  excess  were  placed  in  an  Brlenmeyer  flask 
and  heated  on  a steam  bath  for  one  hour,  a light  yellow  solid 


“IE- 


formed  wlii oh  was  recrystallized  twice  from  95$  alcohol,  li.  p. 
90°. 

Analysis:  $ C.  Bound  64. El.  Gale.  64.73 

$ Hg  found  5,34.  Calc.  5.43 

PxAAGXY  BUTYL  BBGLIDE 

In  a 150  o.c.  Erlenneyer  flask  52  g.  of  phenoxy  butyl 
alcohol  were  placed.  33  g.  of  phosphorous  tribromide  were 
then  added  in  small  amounts.  She  flask  was  cooled  by  means 
of  an  ice  bath.  It  was  allowed  to  stand  for  24  hours  and  then 
heated  on  a steam  bath  for  15  minutes,  The  reaction  mixture 
was  poured  into  water,  agitated,  and  the  oily  layer  separated. 
It  was  distilled  under  diminished  pressure.  50  grams(70$ 
theory) of  phenoxy  butyl  bromide  were  obtained(B.  P.  155-158° 
at  24  mm. ) , The  product  solidified  on  cooling.  M*  P.  400„ 

Analysis:  Wt.  of  sample  .5811  grams 

26.44  c.c,  of  .08513  IT.AgllO^  used 

$ Br2  Pound  34.54.  Gale.  34.89 
T A T.uu.lA T A YLAB A BHOMBDL 

In  a 500  c.c.  ground -glass  stoppered  flask  fitted  with  a 
reflux  condenser  were  placed  68  g.  of  phenoxy  butyl  alcohol 
and  190  c.c.  of  liydrobromic  acia(sp.  gr.  1.57).  The  reaction 
mixture  was  refluxed  for  five  hour’s  after  which  35  c.c.  of 


f 


r 


! 


■ 

J 

i 

i 


-13- 


concentrated  sulfuric  acid  were  added.  2he  refluxing  was  then 
continued  for  five  hours.  200  c.c.  of  water  were  added  and  the 
reaction  mixture  extracted  with  ether.  This  was  washed  with  a 
10p  sodium  hydroxide  solution  and  then  distilled  under  dimin- 
ished pressure.  41  g.(4?^  theory ) of  te tramethylene  bromide  were 
obtained,  boiling  at  93-100°  under  20  mm.  pressure.  34  g. 

(36,j  theory)  of  phenoxy  butyl  bromide  then  distilled  (153-157° 
at  22  mm. ) . 

She  results  of  other  runs  were  as  follows: 

Yield 

Hun  *jnt. alcohol  Aint.48^hBr  Arnt.hr  30^  Dime  2e tramethylene  liienoxy 

Bromide  Butyl 

Bromide 


1 

52 

£>* 

70 

c.c . 

11 

c.c. 

2 

hrs. 

27 fo 

58.5  f0 

2 

50 

g* 

40 

c.c. 

10 

c.c. 

hrs. 

13 $ . 

465?. 

3 

53 

g* 

140 

c.c. 

25 

c.c. 

9 

hrs. 

42  % 

46  fj 

-14- 


iiuinmary 

Lianne  slum  reacts  with  phenoxy  propyl  bromide  to  form 
phenoxy  propyl  magnesium  bromide ( to  a limited  extent ) , un— 
saturated  compound,  and  diphenoxy  hexane* 

nn  attempt  was  made  to  ascertain  the  best  conditions 

offt-chlori  tc  acid* 

A relatively  cheap  method  was  developed  for  the  pre- 
paration of  tetramethylene  bromide  and  phenoxy  butyl  bromide. 


-15- 


Eibliography 

1.  jour.  £.  prakt.  Ch.em.(2)  39,  543(1889) 

2.  Compt.  rend.  152 » 345(1901) 

5.  Ber.  39,  4119(1906) 

4.  ^our.  Biol.  Ch.em.  £7,  443(1916) 

5.  Ber.  24,  2640(1891) 


